Three major groups of drugs currently used for the treatment of pain include opioids, non-steroidal anti-inflammatory drugs (NSAIDs), and analgesic adjuvants. Opioids such as, but not limited to, morphine act at opioid receptors in the brain and spinal cord to block the transmission of pain signals. However, clinical use of opioids is commonly associated with potential abuse and addiction liabilities, the development of tolerance, and other side effects such as constipation, nausea, and cognitive impairments. NSAIDs typically, but not exclusively, block the production of prostaglandins to prevent sensitization of nerve endings that facilitate the pain signal to the brain. NSAIDs effectively treat mild-to-moderate pain with an inflammatory component, but they have a ceiling effect and are not particularly effective in relieving severe or chronic neuropathic pain. Many commonly prescribed over-the-counter NSAIDs cause gastric distress and bleeding, although the newer COX-2 selective NSAIDs may address these side effects liabilities. Analgesic adjuvants, including certain antidepressants, local anesthetics and anticonvulsants, have been shown to be effective in treating some chromic pain states that have not responded to NSAID or opioid therapy.
A substantial number of medical disorders and conditions produce pain as part of the disorder or condition. Relief of this pain is a major aspect of ameliorating or treating the overall disease or condition. One class of pain reliever may not be effective for a particular patient or group of patients. Therefore, a need exists for novel compounds that treat pain through mechanisms different from the established analgesics.
The compounds of the present invention are novel analgesic compounds that bind to nicotinic acetylcholine receptors. In particular, these compounds are active at one or more of the subtypes of neuronal nicotinic receptors including, but not limited to, alpha4beta2, alpha7, and alpha3beta4. The compounds of the present invention have utility in treating pain and can be administered in combination with an opioid such as, but not limited to, morphine, a non-steroid anti-inflammatory agent such as, but not limited to, aspirin, a tricyclic antidepressant, or an anticonvulsant such as, but not limited to, gabapentin or pregabalin for treating pain. The compounds of the present invention have utility for treating disorders associated with the cholinergic system.